Cannabis Sativa For The Pharmaceutical Industry

Euphytica 140: 83–93, 2004. C 2004 Kluwer Academic Publishers. Printed in the Netherlands.

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Cannabinoids for the pharmaceutical industry
Colin G. Stott∗ & Geoffrey W. Guy
GW Pharmaceuticals plc, Porton Down Science Park, Salisbury, Wiltshire SP4 0JQ, UK; (∗author for correspondence: e-mail: cgs@gwpharm.com)

Key words: cannabidiol, cannabinoids, Cannabis sativa L.,delta-9-tetrahydrocannabinol, endocannabinoids, Sativex R

Summary Cannabis sativa, is a rich source of a variety of compounds, including cannabinoids, terpenoids and flavonoids. Their content depends upon the plant genetics, growth conditions, time of harvest and drying conditions. To date, more than 60 different cannabinoids have been identified in the plant. Cannabis has been used medicinally for 4000 years andremained in the British pharmacopaeia until 1932, and in the British Pharmaceutical Codex until 1949. Medical use has been prohibited in the UK since 1973. The principal cannabinoid, delta-9-tetrahydrocannabinol (THC) was first isolated in 1964; the first cannabinoid pharmaceutical product Marinol R (a synthetic THC product) was approved in the USA in 1985. The discovery of specific cannabinoidreceptors in the early 1990s and subsequent identification of the endocannabinoids anandamide and 2-arachadonoylglycerol, led to a resurgence of interest in the field of cannabinoid medicine, especially within the pharmaceutical industry. Cannabidiol (CBD), as a non-psychoactive, cannabinoid is currently a cannabinoid of significant interest, showing a wide range of pharmacological activity. The otherclasses of compounds present in cannabis also have their own pharmacology (e.g. terpenoids, flavonoids). The potential for interaction and synergy between compounds within the plant, may play a role in the therapeutic potential of cannabis. This may explain why a cannabis-based medicine using extracts containing multiple cannabinoids, in defined ratios, and other non-cannabinoid fractions, may providebetter therapeutic success and be better tolerated than the single synthetic cannabinoid medicines currently available. The development and employment of one of these medicines, Sativex R , is described. Abbreviations: AEA: arachidonylethanolamide (anandamide); CBC: cannabichromene; CBD: cannabidiol; CBDA: cannabidiolic acid; CBD-V: cannabidivarin; CBC-V: cannabichromivarin; CBE: cannabielsoin;CBG: cannabigerol; CBL: cannabicyclol; CBN: cannabinol; CBO: cannabitriol; THC: delta-9-tetrahydrocannabinol; THCA: tetrahydrocannabinolic acid; THC-V: tetrahydrocannabivarin; NADA: N-arachidonoyl-dopamine; VAS: visual analogue scale; 2-AG: 2-arachidonoyl-glycerol; 11-OH-THC: 11-hydroxy-tetrahydrocannabinol Introduction Cannabis sativa L. is a rich source of a variety of compounds (in excess of 400),including classes such as cannabinoids, terpenoids and flavonoids. These classes of compounds have their own distinct pharmacology (McPartland & Russo, 2001; Russo & McPartland, 2003). The exact content of the chemical composition of the plant depends upon the plant genetics, growth conditions (nutrition, humidity, light levels) as well as time of harvest, drying conditions (Potter, 2004). Todate, approximately 60 different cannabinoids have been identified in the plant. Cannabis has been used medicinally for 4000 years (Aldrich, 1997; Russo, 2001, 2002) in a variety of cultures and was re-introduced into British medicine in 1842 by W O’Shaughnessy (Grinspoon & Bakalar, 1993). It remained in the British pharmacopaeia until 1932, when cannabis, extract of cannabis and tincture of cannabiswere among 400 medicines removed, though

84 all three remained in the British Pharmaceutical Codex of 1949 (The House of Lords Science and Technology Committee, 1998). However, following the 1961 UN Single Convention on Narcotic Drugs, cannabis and cannabis derivatives became Scheduled products, and were subject to special measures of control and parties could ban their use altogether....